Abstract
Xianglian pill (XLP) is a typical traditional Chinese herbal medicine prescription composed of Coptidis Rhizoma and Aucklandiae Radix. It has been used to treat gastrointestinal disease for centuries. In the present study, the potential mechanisms of XLP in the treatment of ulcerative colitis (UC) were predicted by integrative pharmacology-based approach. Then, the main compounds of XLP were detected by liquid chromatography-mass spectrometry (LC-MS/MS). Finally, we verified the mechanism of XLP in the treatment of UC in a dextran sulfate sodium (DSS) model. C57BL/6 mice were randomly divided into the control group, DSS group, 5-aminosalicylic acid (5-ASA) group which was used as the positive drug control, XLP low, medium, and high dose group, with 10 mice per group. Except for the control group, acute colitis model was induced in the other mice by administering 3% DSS for consecutive 7 days. Mice in 5-ASA and XLP groups were administered with 5-ASA (50 mg/kg) or XLP (0.8, 1.6, 3.2 g/kg) via oral gavage once per day respectively. Body wight and disease activity index were assay during drug intervention. On day 8, all animals in this experiment were sacrificed and colon tissues were collected for analysis after measurement of the length. The results showed that XLP alleviate DSS -induced acute colitis in mice, including inhibition the secretion of pro-inflammatory cytokines, repairing the dysfunction of intestinal epithelial barrier, enhanced autophagy, and blocked the activation of PI3K/Akt/mTOR pathway. Furthermore, inhibiting autophagy by 3-methyladenine attenuated the protective effects of XLP on colitis. The underlying mechanism may be that Xianglian pill promote autophagy by blocking the activation of PI3K/Akt/mTOR signaling pathway.
Highlights
Ulcerative colitis (UC) is an idiopathic inflammatory disorder of the large intestine that starting with mucosal inflammation in the rectum and often extending proximally to involve additional areas of the colon (Rubin et al, 2019)
The goal of for ulcerative colitis (UC) treatment is divided into induction of remission and maintenance of remission according to the clinical activity and the extent of diseases
Xianglian pill (XLP) has been widely used in the treatment of UC in China, but the underlying mechanism remains unclear
Summary
Ulcerative colitis (UC) is an idiopathic inflammatory disorder of the large intestine that starting with mucosal inflammation in the rectum and often extending proximally to involve additional areas of the colon (Rubin et al, 2019). It is one of the two major manifestations of inflammatory bowel disease (IBD), and characterized by imbalanced of cytokines and immune dysfunction and unresolved inflammation associated with intestinal mucosa (Sairenji et al, 2017). Recent studies have shown that UC submucosal inflammation affects the integrity of epithelial barrier structure, which leads to the change of intestinal permeability, promoting the abnormal immune response (Chang et al, 2017). To enhance the function of intestinal mucosal barrier may be a treatment for UC
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